• Share
  • Email
  • Embed
  • Like
  • Save
  • Private Content
Anemia Indian scenario In Chronic Kidney Disease Patients
 

Anemia Indian scenario In Chronic Kidney Disease Patients

on

  • 693 views

this is a comprehensive presentation in Post Doctoral Certificate in Nephrology training program. At Gauhati Medical College Hospital ,Dept Of Nephrology.

this is a comprehensive presentation in Post Doctoral Certificate in Nephrology training program. At Gauhati Medical College Hospital ,Dept Of Nephrology.

Statistics

Views

Total Views
693
Views on SlideShare
693
Embed Views
0

Actions

Likes
1
Downloads
17
Comments
0

0 Embeds 0

No embeds

Accessibility

Categories

Upload Details

Uploaded via as Microsoft PowerPoint

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

    Anemia Indian scenario In Chronic Kidney Disease Patients Anemia Indian scenario In Chronic Kidney Disease Patients Presentation Transcript

    • Anaemia management IndianAnaemia management Indian ScenaroScenaro Presented by-Dr(Lt Col) Ashutosh Ojha, MD PDCDM Student GMCH,Guwahati-32 Moderator-Prof AK Barman Prof & HoD(Nephrology)
    • Estimates of prevalence of CKD inEstimates of prevalence of CKD in the USA: NHANES IIIthe USA: NHANES III StageStage DescriptionDescription GFRGFR (ml/min/1.73(ml/min/1.73 mm22 )) PrevalencePrevalence (%)(%) 11 Kidney damage withKidney damage with normal ornormal or ↑↑ GFRGFR >>9090 3.33.3 22 Kidney damage withKidney damage with mildmild ↓↓ GFRGFR 60–8960–89 3.03.0 33 ModerateModerate ↓↓ GFRGFR 30–5930–59 44.3.3 44 SevereSevere ↓↓ GFRGFR 15–2915–29 0.20.2 55 Kidney failureKidney failure <<15 or15 or (or d(or dialysisialysis)) 0.10.1 Coresh et al AJKD 2003
    • EXTENT OF CKD IN INDIAEXTENT OF CKD IN INDIA India-diabetic capital. Every 5India-diabetic capital. Every 5thth Indian diabetic andIndian diabetic and every 5every 5thth Indian HypertensiveIndian Hypertensive 40-50% of all chronic kidney disease is due to40-50% of all chronic kidney disease is due to diabetesdiabetes Prevalence of CKDPrevalence of CKD Chennai- 0.16Chennai- 0.16 Delhi- 0.78Delhi- 0.78 Incidence of CKDIncidence of CKD  151-232 per million population151-232 per million population (Jha et al)(Jha et al) 785 per million population785 per million population (Agarwal et al)(Agarwal et al)
    • Cause of End Stage Renal DiseaseCause of End Stage Renal Disease (SJMCH)(SJMCH) 10% 40% 28% 18% 4% Diabetics htn IN Others Unknown
    • Challenges in Anaemia ManagementChallenges in Anaemia Management Many patients affected by anaemiaMany patients affected by anaemia 0 5 10 15 20 25 30 35 40 45 50 > 90 60-89 30-59 15-29 Astor et al 2002n=15 625 Patients (%) GFR (mL/min per 1.73 m2 ) 44
    • CKD REGISTRY INDIA
    • CORRECTION OF ANEMIACORRECTION OF ANEMIA TARGET HAEMOGLOBIN =11-12 grams/dl
    • CKD AnaemiaCKD Anaemia Correlates with SurvivalCorrelates with Survival Survival of CKD Patients by Haemoglobin Level Reproduced courtesy of A Levin CKD Anaemia Correlates With Survival Time (months) ProbabilityofSurvival 0 3 6 9 12 15 18 21 24 27 30 33 36 0.70 0.75 0.80 0.85 0.90 0.95 1.00 Baseline haemoglobin Log-Rank Test: p = 0.0001 = 12 - 13 g/dL 11-12 g/dL 10-11 g/dL 10 g/dL 13 g/dL < Survival of CKD Patients by Haemoglobin Level Reproduced courtesy of A Levi
    • Association between renal anaemia andAssociation between renal anaemia and relative risk of death or hospitalisationrelative risk of death or hospitalisation Locatelli et al NDT 2004 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 <10 10–10.9 11–11.9 ≥12 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 <10 10–10.9 11–11.9 ≥12 Relative risk of death Relative risk of hospitalisation RR, overall=0.95 per 1 g/dl higher Hb (p=0.03) RR, overall=0.96 per 1 g/dl higher Hb (p=0.02) 1.22 1.02 1 0.91 1.29 1.09 1 1.07 p=0.06 p=0.86 Ref p=0.49 p<0.001 p=0.14 Ref p=0.44 (n) (1626) (952) (760) (682) (1521) (919) (733) (670) RR Hb (g/dl) at study entry RR Target of 10-12 g/dl is appropriate Renal Anemia correlates with outcome
    • CKD REGISTRY INDIA
    • Problems in anemia management inProblems in anemia management in CKDCKD Common challenges faced are –Common challenges faced are – – Maintenance of stable hemoglobin levels in theirMaintenance of stable hemoglobin levels in their patientspatients – Avoid overshooting Hb targetsAvoid overshooting Hb targets – Balance intravenous iron & EPOBalance intravenous iron & EPO – Improve EPO response to use the lowest effectiveImprove EPO response to use the lowest effective EPO doseEPO dose A major concern is EPO hyporesponsiveness &A major concern is EPO hyporesponsiveness & insufficient iron replacementinsufficient iron replacement IV iron is important in managing theseIV iron is important in managing these challenges to a large extentchallenges to a large extent Kapoian T. Challenge of effectively using erythropoiesis-stimulating agents and intravenous iron. Am J Kidney Dis. 2008 Dec;52(6 Suppl):S21-8.
    • Challenges in Anaemia ManagementChallenges in Anaemia Management Worldwide prevalence and incidenceWorldwide prevalence and incidence of CKDof CKD More than 1.7 million treated with renalMore than 1.7 million treated with renal replacement therapy worldwide in 2004replacement therapy worldwide in 2004 90% patients receiving RRT live in industrialized90% patients receiving RRT live in industrialized countriescountries The incidence of CKD requiring renal replacementThe incidence of CKD requiring renal replacement therapy has doubled over the last 15 yearstherapy has doubled over the last 15 years Dramatically increasing prevalence predicted in the nextDramatically increasing prevalence predicted in the next 10 years largely due to the aging population and10 years largely due to the aging population and increasing incidence of type 2 diabetesincreasing incidence of type 2 diabetes El Nahas & Bello 2005 Grassmann et al 2005
    • 0 100 200 300 400 500 78 80 82 84 86 88 90 92 94 96 98 00 02 Challenges in Anaemia ManagementChallenges in Anaemia Management CKD incidence and prevalenceCKD incidence and prevalence increasingincreasing Prevalent dialysis and transplant (2002: 431 284) Prevalent dialysis (2002: 308 910) Prevalent transplant (2002: 122 374) Incident dialysis and transplant (2002: 100 359) Year No. of patients (thousands) USRDS 2004 Annual Data Report
    • Challenges in Anaemia ManagementChallenges in Anaemia Management Undertreatment of anaemia remainsUndertreatment of anaemia remains Locatelli et al 2004 Pisoni et al 2004 Mean Hb (g/dL) 6 7 8 9 10 11 12 13 Sw eden U SA Spain B elgium C anada Australia /N Z G erm any Italy U K France Japan Prevalent Incident
    • Challenges in Anaemia ManagementChallenges in Anaemia Management Many patients below Hb targetMany patients below Hb target Locatelli et al 2004 Pisoni et al 2004 (%) Patients with Hb <11 g/dL 0 10 20 30 40 50 60 70 80 90 100 Sweden USA Spain Belgium Canada Australia / NZ Germany Italy UK France Japan Prevalent Incident
    • USRDS Kaplan-Meier estimates of the probability of death or a first non-fatal myocardial infarction in the normal- hematocrit groups
    • Mark A. Parazella,MD. CKD series: evaluation and treatment of anemia in chronic kidney disease. Hospital physician. 2003; 31-38,46
    • Mark A. Parazella,MD. CKD series: evaluation and treatment of anemia in chronic kidney disease. Hospital physician. 2003; 31-38,46
    • INDIAN BEST PRACTICEINDIAN BEST PRACTICE GUIDELINESGUIDELINES
    • Anaemia in CRF can be due to multipleAnaemia in CRF can be due to multiple causes, most commonly EPO deficiencycauses, most commonly EPO deficiency and nutritional factors. Since EPO isand nutritional factors. Since EPO is expensive, all efforts must be made toexpensive, all efforts must be made to correct nutritional deficiencies especiallycorrect nutritional deficiencies especially iron deficiency and assessment of otheriron deficiency and assessment of other nutritional factorsnutritional factors.. Indian Best Practices GuidelinesIndian Best Practices Guidelines
    • Guideline 1: Anaemia EvaluationGuideline 1: Anaemia Evaluation (Evidence level A)(Evidence level A)  RBC indices / Peripheral smearRBC indices / Peripheral smear  Iron / TIBC / Ferritin / TranferrinIron / TIBC / Ferritin / Tranferrin saturationsaturation  Stool occult bloodStool occult blood  Stool parasite testStool parasite test  Serum B12 & Red cell folateSerum B12 & Red cell folate concentrationsconcentrations
    • Guideline 1 (a): Anaemia EvaluationGuideline 1 (a): Anaemia Evaluation  RBC indices / Peripheral smearRBC indices / Peripheral smear  Iron / TIBC / Ferritin / TranferrinIron / TIBC / Ferritin / Tranferrin saturationsaturation  Stool occult bloodStool occult blood  Stool parasite testStool parasite test A fuller work up should also include theA fuller work up should also include the followingfollowing as indicated.as indicated.  Serum B12 and red cell folateSerum B12 and red cell folate concentrationsconcentrations
    • Guideline 1 (a): Anaemia EvaluationGuideline 1 (a): Anaemia Evaluation (contd..)(contd..)  Serum and / or urine protein electrophoresis /Serum and / or urine protein electrophoresis / immunoblottingimmunoblotting (where available).(where available).  Serum aluminiumSerum aluminium  Bone marrow examination in selected casesBone marrow examination in selected cases  Assessment of occult gastrointestinal blood loss.Assessment of occult gastrointestinal blood loss. Elements of this work up will be necessary if there isElements of this work up will be necessary if there is clinical suspicion of primary haematological disorderclinical suspicion of primary haematological disorder (haemolysis, marrow dysplasia), macrocytosis,(haemolysis, marrow dysplasia), macrocytosis, aluminium poisoning or occult blood loss).aluminium poisoning or occult blood loss). (Evidence level A)
    • Guideline 2(a): Diagnosis of AnaemiaGuideline 2(a): Diagnosis of Anaemia of Chronic Renal Failureof Chronic Renal Failure  No cause other than CRF by aboveNo cause other than CRF by above investigation.investigation.  GFR <30 in non-diabetics and 45ml/min. inGFR <30 in non-diabetics and 45ml/min. in diabetic patients (S. creat >2mg/dl).diabetic patients (S. creat >2mg/dl).  Measurement of plasma EPO concentrationMeasurement of plasma EPO concentration notnot indicated.indicated.
    • Guideline 7: What are the causesGuideline 7: What are the causes of inadequate response to EPOof inadequate response to EPO (contd..)(contd..) vi)vi) HemolysisHemolysis VVii)ii) Osteitis fibrosaOsteitis fibrosa viii)viii) Aluminium toxicityAluminium toxicity ix)ix) Haemoglobinopathies (e.g. alpha & BetaHaemoglobinopathies (e.g. alpha & Beta thalassemias, sickle cell anaemia)thalassemias, sickle cell anaemia) x)x) Multiple myeloma & other malignancies.Multiple myeloma & other malignancies. xi)xi) Use of ACE-1 / ARB agentsUse of ACE-1 / ARB agents
    • Guideline 7(a): Resistance to EPO /Guideline 7(a): Resistance to EPO / inadequate response to EPOinadequate response to EPO  Failure to achieve target Hb concentrationFailure to achieve target Hb concentration a)a) While receiving more than 300IU/kg/week S.C orWhile receiving more than 300IU/kg/week S.C or 450units IU/kg/week IV.450units IU/kg/week IV. b) Continued need for such dosage to maintain targetb) Continued need for such dosage to maintain target in presence of adequate iron stores.in presence of adequate iron stores.  Resistance (hypo responsiveness) is relativeResistance (hypo responsiveness) is relative  In the absence of detectable abnormalities of any oneIn the absence of detectable abnormalities of any one of the above conditions – marrow examination isof the above conditions – marrow examination is indicated (for diagnosis of resistance) includingindicated (for diagnosis of resistance) including haematologist reference.haematologist reference.
    • ROLE OF IRONROLE OF IRON
    • Need for IV iron in CKDNeed for IV iron in CKD Iron deficiency in CKD patients develops primarily duringIron deficiency in CKD patients develops primarily during the correction of renal anemia by EPO treatmentthe correction of renal anemia by EPO treatment Among ESRD patients receiving EPO,Among ESRD patients receiving EPO, more than 50%more than 50% are iron deficientare iron deficient Approximately 150 mg of iron is necessary for anApproximately 150 mg of iron is necessary for an increase of 1 g/dl in hemoglobin levelincrease of 1 g/dl in hemoglobin level Causes of anemia in CKD patients include –Causes of anemia in CKD patients include – – Inadequate intake of dietary ironInadequate intake of dietary iron – Blood loss during the extracorporeal procedure GI bleedingBlood loss during the extracorporeal procedure GI bleeding – Inadequate intestinal iron absorption and inhibition of iron releaseInadequate intestinal iron absorption and inhibition of iron release from macrophagesfrom macrophages – Increased iron requirements during therapy withIncreased iron requirements during therapy with erythropoiesis-erythropoiesis- stimulating agents (ESAs).stimulating agents (ESAs). 1. Horl WH. Iron therapy for renal anemia: how much needed, how much harmful? Pediatr Nephrol 2007;22:480–9. 2. Guidelines for anemia of chronic kidney disease. NKF K/DOQI guidelines 2000. Available at: http://www.kidney.org/PROFESSIONALS/kdoqi/guidelines_updates/doqiupan_iii.html#5
    • IV iron in CKDIV iron in CKD IV iron therapy is superior to oral ironIV iron therapy is superior to oral iron supplementation in CKDsupplementation in CKD Risk factors associated with IV iron therapyRisk factors associated with IV iron therapy acute allergic reactionsacute allergic reactions long-termlong-term complications caused by thecomplications caused by the generation ofgeneration of powerful oxidant species,powerful oxidant species, Allergy is to related toAllergy is to related to dextran moietydextran moiety Iron dextran is associated with higher incidenceIron dextran is associated with higher incidence of Type I hypersensitivity than Iron sucroseof Type I hypersensitivity than Iron sucrose Iron sucrose carries the lowest risk forIron sucrose carries the lowest risk for hypersensitivityhypersensitivity 1. Horl WH. Iron therapy for renal anemia: how much needed, how much harmful? Pediatr Nephrol 2007;22:480–9.
    • Iron sucrose in kidney diseaseIron sucrose in kidney disease Iron deficiency may be corrected by oral ironIron deficiency may be corrected by oral iron supplementation but it is limited by –supplementation but it is limited by – – Poor compliancePoor compliance – Adverse gastrointestinal reactionsAdverse gastrointestinal reactions IV iron preparations commonly used includeIV iron preparations commonly used include iron sucrose, sodium ferric gluconate, & ironiron sucrose, sodium ferric gluconate, & iron dextrandextran Iron sucrose is safer than iron dextran, isIron sucrose is safer than iron dextran, is generally considered a safe and effective IVgenerally considered a safe and effective IV iron preparation in renal anemiairon preparation in renal anemia 1. Li H. Intravenous iron sucrose in peritoneal dialysis patients with renal anemia. Peritoneal Dialysis International 2008;28:149–54.
    • Iron sucrose in kidney diseaseIron sucrose in kidney disease Iron sucrose is a novel and effective addition inIron sucrose is a novel and effective addition in the management of ‘Anemia related to kidneythe management of ‘Anemia related to kidney diseases’diseases’ Iron Sucrose is elemental iron whichIron Sucrose is elemental iron which replenishes body iron stores in patients withreplenishes body iron stores in patients with iron deficiencyiron deficiency Approximately 25% of hemodialysis patientsApproximately 25% of hemodialysis patients can be maintained on oral ironcan be maintained on oral iron supplementation; the others require IV ironsupplementation; the others require IV iron supplementationsupplementation 1. Dennis J. Cada. Iron Sucrose Injection. Drug Reviews From The Formulary, Volume 36, April 2001,404-412 2. W.H. Horl, OPTA-therapy with iron and erythropoiesis-stimulating agents in chronic kidney disease, nephrology dial transplant. 2007 suppl 3;iii2-iii6
    • IndicationsIndications IV iron sucrose is indicated in –IV iron sucrose is indicated in – – Non-Dialysis Dependent - Chronic Kidney Disease (NDD-Non-Dialysis Dependent - Chronic Kidney Disease (NDD- CKD) patients receiving an erythropoietinCKD) patients receiving an erythropoietin – Non-Dialysis Dependent - Chronic Kidney Disease (NDD-Non-Dialysis Dependent - Chronic Kidney Disease (NDD- CKD) patients not receiving an erythropoietinCKD) patients not receiving an erythropoietin – Hemodialysis Dependent - Chronic Kidney Disease (HDD-Hemodialysis Dependent - Chronic Kidney Disease (HDD- CKD) patients receiving an erythropoietinCKD) patients receiving an erythropoietin – Peritoneal Dialysis Dependent - Chronic Kidney DiseasePeritoneal Dialysis Dependent - Chronic Kidney Disease (PDD-CKD) patients receiving an erythropoietin(PDD-CKD) patients receiving an erythropoietin 1. Venofer® [package insert]. Shirley, NY: American Regent, Inc.; 2007. 2. Hollands JM et al. Safety of High-Dose Iron Sucrose Infusion in Hospitalized Patients With Chronic Kidney Disease. Am J Health-Syst Pharm. 2006;63(8):731-734. 3. Mircescu G et al. Intravenous iron supplementation for the treatment of anaemia in pre-dialyzed chronic renal failure patients. Nephrol Dial Transplant 2006;21:120-4.
    • Iron sucrose in pre-dialysis CRFIron sucrose in pre-dialysis CRF patientspatients Patients undergoing chronicPatients undergoing chronic hemodialysis often present with anemiahemodialysis often present with anemia IV iron therapy is administered inIV iron therapy is administered in conjunction with EPO as it helps preventconjunction with EPO as it helps prevent EPO-hypo-responsivenessEPO-hypo-responsiveness Study evaluated use of Iron sucrose inStudy evaluated use of Iron sucrose in pre dialyzed patients of CRFpre dialyzed patients of CRF 60 non-diabetic CRF patients were60 non-diabetic CRF patients were included in the studyincluded in the study Mircescu G ,et al. Intravenous iron supplementation for the treatment of anaemia in pre-dialyzed chronic renal failure patients. Nephrol Dial Transplant 2006;21:120-4.
    • ResultsResults 60 patients included in the study60 patients included in the study 58% of patients reporting a rise in Hb > 1 g/dL vs. baseline in the study58% of patients reporting a rise in Hb > 1 g/dL vs. baseline in the study 80% of patients had a Hb > 10 g/dL vs. 44% at baseline80% of patients had a Hb > 10 g/dL vs. 44% at baseline 55% had a Hb > 11 g/dL vs. 0% at baseline55% had a Hb > 11 g/dL vs. 0% at baseline Mean serum iron concentration increased from –Mean serum iron concentration increased from – – 73.973.9 µµg/dL at baselineg/dL at baseline – 84.284.2 µµg/dL at 6 monthsg/dL at 6 months – 101.8101.8 µµg/dL at 12 months of therapyg/dL at 12 months of therapy No worsening of renal function, and no adverse events were reportedNo worsening of renal function, and no adverse events were reported Mircescu G et al. Intravenous iron supplementation for the treatment of anaemia in pre- dialyzed chronic renal failure patients. Nephrol Dial Transplant 2006;21:120-4. Serum Iron concentration Baseline 6 months 12 months 0 10 20 30 40 50 60 70 80 90 100 110 Mean Serum Fe concentration Time line MeanserumFeConc.
    • Efficacy of Iron sucrose inEfficacy of Iron sucrose in hemodialysis patientshemodialysis patients Schiesser et al conducted a prospectiveSchiesser et al conducted a prospective multicentre clinical trial in 50 iron-multicentre clinical trial in 50 iron- replete hemodialysis patients toreplete hemodialysis patients to evaluate the efficacy of iron sucroseevaluate the efficacy of iron sucrose administration for 6 monthsadministration for 6 months Hb level remained stable (12Hb level remained stable (12±±1.1 at1.1 at baseline & 12.1baseline & 12.1±±1.5 g/dl at the end of1.5 g/dl at the end of the study)the study) Reduced dose for EPOReduced dose for EPO Schiesser et al. Weekly low-dose treatment with intravenous iron sucrose maintains iron status and decreases epoetin requirement in iron- replete haemodialysis patients. Nephrol Dial Transplant (2006) 21: 2841–5.
    • Iron sucrose IV reduces EPOIron sucrose IV reduces EPO demand in dialysis patientsdemand in dialysis patients In the study of Iron sucrose inIn the study of Iron sucrose in hemodialysis patients conducted byhemodialysis patients conducted by Schiesser et al the dosage for the threeSchiesser et al the dosage for the three different epoetins decreased by –different epoetins decreased by – – 38.5% with darbepoetin alfa38.5% with darbepoetin alfa – 6.3% with epoetin alfa6.3% with epoetin alfa – 8.3% with epoetin beta8.3% with epoetin beta Schiesser et al. Weekly low-dose treatment with intravenous iron sucrose maintains iron status and decreases epoetin requirement in iron-replete haemodialysis patients. Nephrol Dial Transplant (2006) 21: 2841–5.
    • Results showing reduced EPOResults showing reduced EPO need with iron sucroseneed with iron sucrose Schiesser et al showed reduced EPOSchiesser et al showed reduced EPO need with low dose maintenance ironneed with low dose maintenance iron sucrose in their studysucrose in their study Schiesser et al. Weekly low-dose treatment with intravenous iron sucrose maintains iron status and decreases epoetin requirement in iron-replete haemodialysis patients. Nephrol Dial Transplant (2006) 21: 2841–5.
    • IV iron reduces EPO demand inIV iron reduces EPO demand in dialysis patientsdialysis patients Chang et al studies the beneficial effects of 2Chang et al studies the beneficial effects of 2 weekly IV iron supplementation compared to onceweekly IV iron supplementation compared to once monthly IV iron in 149 iron replete patientsmonthly IV iron in 149 iron replete patients EPO requirementEPO requirement reduced by 25%reduced by 25% when sereumwhen sereum ferritin & Transferrin saturation was maintained atferritin & Transferrin saturation was maintained at high levels by administering 2 weekly IV ironhigh levels by administering 2 weekly IV iron compared to IV iron given once monthlycompared to IV iron given once monthly Significant decrease in serum albumin, cholesterolSignificant decrease in serum albumin, cholesterol & pre-dialysis creatinine when IV iron was& pre-dialysis creatinine when IV iron was administered 2 weekly for 1 yearadministered 2 weekly for 1 year Chang CH et al. Reduction in erythropoietin doses by the use of chronic intravenous iron supplementation in iron-replete hemodialysis patients. Clin Nephrol. 2002;57:136-41.
    • IV iron reduces EPO demand in dialysisIV iron reduces EPO demand in dialysis patients – Results from Meta analysispatients – Results from Meta analysis Compared to oral iron IV iron preparations significantlyCompared to oral iron IV iron preparations significantly reduce the EPO requirement in dialysis patientsreduce the EPO requirement in dialysis patients Rozen-Zvi et al. Intravenous Versus Oral Iron Supplementation for the Treatment of Anemia in CKD: Systematic Review and Meta-analysis. American Journal of Kidney Diseases 2008;52:897-906.
    • Iron sucrose in CKD patients not onIron sucrose in CKD patients not on dialysisdialysis Charytan et al compared oral iron withCharytan et al compared oral iron with Iron sucrose in 96 NDD-CKD patientsIron sucrose in 96 NDD-CKD patients More IV iron patients (54.2%) attainedMore IV iron patients (54.2%) attained hemoglobin values > 11.0 g/dlhemoglobin values > 11.0 g/dl compared to oral iron patients (31.3%)compared to oral iron patients (31.3%) There were no serious side effects withThere were no serious side effects with iron sucroseiron sucrose Charytan C et al. Comparison of intravenous iron sucrose to oral iron in the treatment of anemic patients with chronic kidney disease not on dialysis. Nephron Clin Pract. 2005;100(3):c55-62.
    • Efficacy & safety of Iron sucrose inEfficacy & safety of Iron sucrose in peritoneal dialysis patientsperitoneal dialysis patients Li et al conducted a study to compare the clinicalLi et al conducted a study to compare the clinical outcomes & safety of IV iron sucrose & oral ferrousoutcomes & safety of IV iron sucrose & oral ferrous succinate in combination with rHuEPO therapy insuccinate in combination with rHuEPO therapy in patients on maintenance PDpatients on maintenance PD 46 patients were included – 26 received iron sucrose &46 patients were included – 26 received iron sucrose & 20 oral20 oral ironiron Hb & Hct increased significantly at 2 weeks in the IVHb & Hct increased significantly at 2 weeks in the IV group compared with baselinegroup compared with baseline The total response rate at 8 weeks was 94.8% for the IVThe total response rate at 8 weeks was 94.8% for the IV group - significantly higher than that of the oral groupgroup - significantly higher than that of the oral group (55.0%)(55.0%) There were no adverse events with IV ironThere were no adverse events with IV iron 8 patients in the oral group had adverse GI effects8 patients in the oral group had adverse GI effects Li H. Intravenous iron sucrose in peritoneal dialysis patients with renal anemia. Peritoneal Dialysis International 2008;28:149–54.
    • Results of Iron sucrose in PDResults of Iron sucrose in PD patients contd.patients contd. Response rates to IV iron sucroseResponse rates to IV iron sucrose therapy compared to Oral iron therapytherapy compared to Oral iron therapy Li H. Intravenous iron sucrose in peritoneal dialysis patients with renal anemia. Peritoneal Dialysis International 2008;28:149–54.
    • Efficacy of Iron sucrose in ESRDEfficacy of Iron sucrose in ESRD Iron sucrose in apparently iron-repleteIron sucrose in apparently iron-replete patients will decrease the EPOpatients will decrease the EPO requirements for a given targetrequirements for a given target hematocrit in patients on maintenancehematocrit in patients on maintenance hemodialysis with end-stage renalhemodialysis with end-stage renal disease (ESRD)disease (ESRD) 1. Schiesser et al. Weekly low-dose treatment with intravenous iron sucrose maintains iron status and decreases epoetin requirement in iron-replete haemodialysis patients. Nephrol Dial Transplant (2006) 21: 2841–2845. 2. Shaldon S. The use of IV iron in the treatment of anaemia of ESRD patients on maintenance haemodialysis: an historical and personal view. Nephrol Dial Transplant (2007) 22: 23–25.
    • Safety of Iron sucroseSafety of Iron sucrose Aronoff et al studied the safety of ironAronoff et al studied the safety of iron sucrose in hemodialysis patientssucrose in hemodialysis patients 665 hemodialysis patients with 80 who665 hemodialysis patients with 80 who had experienced previous intolerance tohad experienced previous intolerance to other IV iron preparations were given ironother IV iron preparations were given iron sucrosesucrose There were no serious or life-threateningThere were no serious or life-threatening drug-related adverse eventsdrug-related adverse events Aronoff GR et al. Iron sucrose in hemodialysis patients: Safety of replacement and maintenance regimens. Kidney International, 2004;66:1193–8.
    • Iron sucrose in patientsIron sucrose in patients hypersensitive to iron dextranhypersensitive to iron dextran Iron dextran has been the onlyIron dextran has been the only available parenteral ironavailable parenteral iron preparation for a long timepreparation for a long time Its use has been associated withIts use has been associated with increased risk of allergic reactions,increased risk of allergic reactions, even after reaction-free previouseven after reaction-free previous useuse Haddad A et al. Use of Iron Sucrose in Dialysis Patients Sensitive to Iron Dextran. Saudi J Kidney Dis Transpl 2009;20(2):208-211
    • Safety of Iron sucrose comparedSafety of Iron sucrose compared to other iron preparationsto other iron preparations Rates of life-threatening ADEs –Rates of life-threatening ADEs – 1.1. 0.6 per million for iron0.6 per million for iron sucrosesucrose 2.2. 0.9 per million for sodium0.9 per million for sodium ferric gluconate complexferric gluconate complex 3.3. 3.3 per million for lower3.3 per million for lower molecular weight iron dextranmolecular weight iron dextran 4.4. 11.3 per million per million for11.3 per million per million for higher molecular weight ironhigher molecular weight iron dextrandextran Chertow GM et al. Update on adverse drug events associated with parenteral iron. Nephrol Dial Transplant (2006) 21: 378–382. Safety of Iron preparations 1 2 3 4 0 1 2 3 4 5 6 7 8 9 10 11 12 Iron preparations ADEpermillion
    • Dosing and administrationDosing and administration NDD-CKD - ANDD-CKD - Administered as a total cumulativedministered as a total cumulative dose of 1,000 mg over a 14 days as a 200 mgdose of 1,000 mg over a 14 days as a 200 mg slow IV injection undiluted over 2 to 5 minutesslow IV injection undiluted over 2 to 5 minutes on 5 different occasions.on 5 different occasions. HDD-CKD - AHDD-CKD - Administered undiluted as a 100dministered undiluted as a 100 mg slow IV over 2 to 5 minutes or as anmg slow IV over 2 to 5 minutes or as an infusion of 100 mg, diluted in a maximum of 100infusion of 100 mg, diluted in a maximum of 100 mL of NS over 15 minutes per consecutivemL of NS over 15 minutes per consecutive hemodialysis session for a total cumulativehemodialysis session for a total cumulative dose of 1,000 mg.dose of 1,000 mg. 1. Venofer® [package insert]. Shirley, NY: American Regent, Inc.; 2007.
    • Dosing and administration contd.Dosing and administration contd. PDD-CKD - APDD-CKD - Administered undiluted as a totaldministered undiluted as a total cumulative dose of 1,000 mg in 3 divided doses,cumulative dose of 1,000 mg in 3 divided doses, given by slow IV infusion, over 28 days:given by slow IV infusion, over 28 days: – 2 infusions of 300 mg over 1.5 hs 14 days apart2 infusions of 300 mg over 1.5 hs 14 days apart – Followed by 1 400 mg infusion over 2.5 h 14 days laterFollowed by 1 400 mg infusion over 2.5 h 14 days later – Should be diluted in 250 mL of NSShould be diluted in 250 mL of NS Low maintenance doses in hemodialysisLow maintenance doses in hemodialysis patients include 50mg injected into the venouspatients include 50mg injected into the venous limb of the haemodialysis tubing system (slowlimb of the haemodialysis tubing system (slow intravenous push at a rate of 10 mg/min)intravenous push at a rate of 10 mg/min) 1. Venofer® [package insert]. Shirley, NY: American Regent, Inc.; 2007.
    • Dosing and administration contd.Dosing and administration contd. The usual dose is 100 mg administered one toThe usual dose is 100 mg administered one to three times per week.three times per week. Most patients will require a minimumMost patients will require a minimum cumulative dose of 1000 mg of elemental ironcumulative dose of 1000 mg of elemental iron administered over 10 sequential dialysisadministered over 10 sequential dialysis sessions to achieve a favorable responsesessions to achieve a favorable response Patients may continue to receive IV ironPatients may continue to receive IV iron therapy at the lowest dose necessary totherapy at the lowest dose necessary to maintain target levels of hemoglobin,maintain target levels of hemoglobin, hematocrit & iron storage parametershematocrit & iron storage parameters Cada DJ. Iron Sucrose Injection. Hospital Pharmacy 2001;36:404–12.
    • Monitoring parametersMonitoring parameters Patients receiving regular IV iron therapy requirePatients receiving regular IV iron therapy require monitoring of hematologic parameters & iron indices (Hb,monitoring of hematologic parameters & iron indices (Hb, Hct, TSAT, & ferritin)Hct, TSAT, & ferritin) Maintain TSAT between 20% and 50%Maintain TSAT between 20% and 50% Iron therapy should be withheld in patients with TSATIron therapy should be withheld in patients with TSAT ≥50%≥50% Iron therapy should be withheld in patients with ferritinIron therapy should be withheld in patients with ferritin values ≥800 ng/mLvalues ≥800 ng/mL Since transferrin saturation values increase rapidly afterSince transferrin saturation values increase rapidly after IV administration of iron sucrose, serum iron values mayIV administration of iron sucrose, serum iron values may be reliably obtained 48 hours after IV iron sucrose dosingbe reliably obtained 48 hours after IV iron sucrose dosing Cada DJ. Iron Sucrose Injection. Hospital Pharmacy 2001;36:404–12.
    • INDIAN BEST PRACTICEINDIAN BEST PRACTICE GUIDELINES … contdGUIDELINES … contd
    • Guideline 9: When to assess ironGuideline 9: When to assess iron status after EPO therapystatus after EPO therapy 1)1) Iron status must be assessed once in 3Iron status must be assessed once in 3 months while on EPO therapy.months while on EPO therapy.
    • Guideline 9(a): When to assessGuideline 9(a): When to assess iron status after EPO therapy?iron status after EPO therapy?  CKD patients should have sufficientCKD patients should have sufficient iron stores to maintain target Hb%iron stores to maintain target Hb% (Evidence).(Evidence).  To achieve this, sufficient iron to beTo achieve this, sufficient iron to be administered.administered. to maintain TSAT>20%to maintain TSAT>20% Ferritin >100ng/mlFerritin >100ng/ml
    • Guideline 9(a): When to assess ironGuideline 9(a): When to assess iron status after EPO therapy?status after EPO therapy? (contd..)(contd..)  To achieve this level, aim atTo achieve this level, aim at - TSAT 30-40%- TSAT 30-40% - Ferritin 200-500ng/ml- Ferritin 200-500ng/ml (Evidence level B)(Evidence level B)  No benefit is achieved if TSAT >50% & serumNo benefit is achieved if TSAT >50% & serum ferritin >800ng/ml and iron should not beferritin >800ng/ml and iron should not be administered beyond this level (Evidence B)administered beyond this level (Evidence B)
    • Monitoring iron stores &Monitoring iron stores & supplement Ironsupplement Iron 1.1. During initiation of EPO & increased doseDuring initiation of EPO & increased dose of EPO.of EPO. TSAT / serum ferritin to be checked every monthTSAT / serum ferritin to be checked every month in patients not receiving IV iron or once in threein patients not receiving IV iron or once in three months in those receiving IV iron (opinion).months in those receiving IV iron (opinion). 2.2. Once target Hb% achieved, check iron storesOnce target Hb% achieved, check iron stores once in 3 months.once in 3 months.
    • Monitoring iron stores &Monitoring iron stores & supplement Ironsupplement Iron (contd..)(contd..) 3.3. In doses of not more than 125mg IV Dextran, noIn doses of not more than 125mg IV Dextran, no interruption of treatment to check iron stores (Evidence).interruption of treatment to check iron stores (Evidence). 4.4. However with large doses (1000mg IV Dextran), a gap ofHowever with large doses (1000mg IV Dextran), a gap of 2 weeks after stopping IV iron, to be ensured to check2 weeks after stopping IV iron, to be ensured to check stores (Evidence).stores (Evidence). 5.5. CKD patients not treated with EPO with TSAT >20%,CKD patients not treated with EPO with TSAT >20%, ferritin >100ng/ml, Iron stores to be checked once 3-6ferritin >100ng/ml, Iron stores to be checked once 3-6 months (opinion).months (opinion).
    • Key pointsKey points Anemia in CKD patients is commonAnemia in CKD patients is common EPO therapy forms the mainstay ofEPO therapy forms the mainstay of treatmenttreatment EPO therapy alone may be ineffectiveEPO therapy alone may be ineffective unless supplemented by ironunless supplemented by iron Oral iron supplementation has problems ofOral iron supplementation has problems of intoleranceintolerance IV iron forms the best adjunct with EPO inIV iron forms the best adjunct with EPO in CKD patients.CKD patients.
    • Key pointsKey points IV iron sucrose is one of the iron preparationsIV iron sucrose is one of the iron preparations It is indicated in hemodialysis patients, nonIt is indicated in hemodialysis patients, non hemodialysis patients with or without EPO andhemodialysis patients with or without EPO and peritoneal dialysis patientsperitoneal dialysis patients Efficacy is proved in each of these indicationsEfficacy is proved in each of these indications Low maintenance dose of Iron sucrose keepsLow maintenance dose of Iron sucrose keeps Hb and Hct stable in hemodialysis patientsHb and Hct stable in hemodialysis patients
    • Key pointsKey points Iron sucrose administration along withIron sucrose administration along with EPO reduces the dose requirement ofEPO reduces the dose requirement of EPOEPO Iron sucrose can be safely given toIron sucrose can be safely given to patients hypersensitive to iron dextranpatients hypersensitive to iron dextran Iron sucrose is safer than other IV ironIron sucrose is safer than other IV iron preparationspreparations
    • n = 56 n = 45 Laboratory and transfusion dataLaboratory and transfusion data Parameter HD (n=157) PD (n=126) P value Hemoglobin (g/dl) 10.47 10.71 0.45 Serum ferritin (g/dl) 258.7 253.8 0.77 Transferrin saturation (%) 28.5 28.1 0.94 Mean number of transfusions (units) 4.59 2.17 0.01 % of patients receiving at least one transfusion 52.9% 40.9% 0.01 % of patients receiving transfusion if requiring between 6,000 and 10,000 units rHuEpo per week 59.5% 37.5% 0.02 House AA, et al, Nephrol Dial Transplant, 1998; 13:1763-1769 Patients receiving renal replacement therapy with HDPatients receiving renal replacement therapy with HD received more blood transfusions and more rHuEpo toreceived more blood transfusions and more rHuEpo to maintain the same hemoglobin as compared to those treatedmaintain the same hemoglobin as compared to those treated with PD.with PD. Conclusion:Conclusion:
    • n = 56 n = 45 Patients on EPO n = 56 n = 45 n = 56 Gokulnath et al, IJPD,16:22-28;2008
    • n = 56 n = 45 Patients on EPO n = 56 n = 56 n = 45 Gokulnath et al, IJPD,16:22-28;2008
    • n = 56 n = 45 Patients on EPO (IU/kg/wk) n = 56 n = 45 n = 56 n = 45 n = 56 Gokulnath et al, IJPD,16:22-28;2008
    • n = 56 n = 45 Patients on Serum Iron (mg) n = 56 n = 45 n = 56 n = 45 n = 56 n = 45 n = 56 Gokulnath et al, IJPD,16:22-28;2008
    • n = 56 n = 45 Cohort followed up 30 months Blood Transfusions in patients onBlood Transfusions in patients on Maintenance HD / CAPDMaintenance HD / CAPD Gokulnath et al, IJPD,16:22-28;2008
    • STEM CELL THERAPYSTEM CELL THERAPY FUTURE?FUTURE?
    • Thank youThank you